AIDS VIRUS
Acquired Immunodeficiency Syndrome (AIDS) is a disease characterized by severe immune deficiency due primarily to impairment of the patient's cell mediated immune response (Gottlieb, M., et al., 1981, N. Engl. J. Med. 305:1425; Masur, J., et. al., 1981, N. Engl. J. Med. 305:1431). Two clinical presentations of the disease are recognized: (a) a prodromal phase called Lymphadenopathy Syndrome (LAS) characterized by chronic lymphadenopathy, leukopenia and a quantitative decrease in peripheral blood helper cells (OKT4 cells) leading to a reversal of the normal peripheral helper to suppressor T lymphocyte ratio (OKT4:OKT8) which shifts from 2 to 0.1 or less as the disease progresses; and (b) an immuno-deficient state termed AIDS characterized by a decrease in OKT4 cells and reversal of the normal OKT4:OKT8 ratio, absolute lymphopenia, and repetitive opportunistic infections mainly by Pneumocystis carnii; this latter phase is ultimately associated with death in the majority of cases. Certain subsets of patients have increased incidence of lymphoma and Kaposi's sarcoma. Currently, there is no cure for the disease.
Epidemiological data along with information concerning the types of patients that acquired the disease suggested that an infectious agent transmitted by intimate contact might be the cause of the disease. Subsequently three groups have provided strong evidence that the causative agent of AIDS is a retrovirus with a tropism for helper T lymphocytes. These groups are:
Although all three viruses were isolated independently, they all probably belong to the same retrovirus subgroup (Levy, J. A., et al., 1984, Science 225:840) and will be collectively referred to herein as LAV/HTLV III.
The general structure of retroviruses is that of a ribonucleoprotein core surrounded by a lipid containing envelope which the virus acquires during the course of cell budding. Embedded within the envelope and projecting outward are the viral encoded glycoproteins. These determine the host range of the virus and react with specific receptors on the surface of susceptible cells. Neutralizing antibodies are thought to bind to envelope glycoproteins and block their interaction with receptors on the surface of cells (pp. 534-535 in, The Molecular Biology of Tumor Viruses, ed. John Tooze, 1973, Cold Spring Harbor Laboratory; pp. 226-227 and 236-237 in, RNA Tumor Viruses, ed. R. Weiss, N. Teich, H. Varmus, and J. Coffin, 1982, Cold Spring Harbor Laboratory.). In the specific case of LAV/HTLV III, there is evidence that the T.sub.4 antigen, present on a subset of T-lymphocytes, is the receptor or a component of the receptor for the virus (Dalgleish, A. G., et al., 984, Nature 312:763; Klatzmann, D., et al., 1984, Nature 12:767).
The RNA genome of LAV/HTLV III contains the gag gene, which codes for the internal structural proteins (core proteins) of the virus and defines the viral group-specific antigens, the pol gene, which codes for the virion associated reverse transcriptase, and the env gene, which codes for the viral glycoproteins. Other regions such as sor and 3'-orf denote areas of the genome containing open reading frames; the function of these regions is not known at present.